This proposal describes the development of the novel principle that agonists of the adenosine 3 receptor have broad anti-inflammatory potential. The proposal presents evidence that an agonist of the adenosine 3 (A3) receptor, namely N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA); (1) reduces the production of multiple pro-inflammatory cytokines and chemokines; (2) enhances the production of the anti-inflammatory cytokine IL-10; (3) inhibits the expression of the inducible isoform of nitric oxide synthase and (4) protects in rodent models of arthritis. The specific aims of the current proposal are to explore the efficacy of orally administered IB-MECA in the rodent arthritis model and to obtain preliminary toxicity data of this A3 receptor agonist. Phase II studies will focus on additional pre-clinical pharmaceutical testing to support a regulatory filing for human clinical trials. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE